The effect of platelets on invasiveness and protease production of human mammary tumor cells

Abstract

Interaction of tumor cells with platelets facilitates metastasis of tumor cells. It has been proposed that platelets protect tumor cells against the host's immune defense and enhance tumor-cell extravasation. In the present work we show that platelets increase the invasiveness of 3 mammalian cell lines (MCF-7, ZR-51 and MDA-MB231) through extracellular matrix, and propose this as an additional mechanism by which platelets facilitate metastasis. Since gelatinase and urokinase have both been implicated in degradation of the extracellular matrix and cell migration, and therefore in tumor invasion, we have also analyzed whether the interaction of platelets with tumor cells can modify the secretion of these proteases by tumor cells. MDA-MB231, which was the most invasive cell line among the 3 tested and was the most potent in inducing platelet aggregation, secreted the highest level of urokinase and was the only one in which gelatinase was detected. While platelets had no significant effect on the urokinase activity expressed by these cells, they induced in MDA-MB231 an important increase in the secretion of gelatinase, which can be reproduced by both platelet membrane and platelet releasate of activated platelets. This increase in gelatinase could be responsible, at least in part, for the increased invasiveness of these cells, since added TIMP-1 significantly reduced the number of cells which traversed matrigel.

Gene Expression of Angiogenic Factors Correlates with Metastatic Potential of Prostate Cancer Cells

“…Inhibition of MMP activity by TIMPs preserves the extracellular matrix, thereby inhibiting tumor invasion. Thus, the equilibrium between the activities of MMPs and TIMPs in tumor tissue may be an important factor regulating tumor invasion and metastasis (42,43). Our study shows constitutive expression of TIMP-1, TIMP-3, and TIMP-4 in all three cell lines investigated.…”

Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer

“…Third, because of the leaky vasculature of angiogenic tumors (36), platelets are in contact with tumor cells and are therefore able to secrete multiple factors upon activation (37). Fourth, MDA-MB-231 breast cancer cells (as well as other tumor cell lines) interact with platelets and stimulate platelet aggregation in vitro (38), suggesting that the platelet-aggregating activity of breast cancer cells might induce the release of LPA from activated platelets. In agreement with the latter findings (38), we observed here that our MDA-BO2 parental and transfected breast cancer cell lines strongly stimulated platelet aggregation and the subsequent release of LPA from activated platelets.…”

“…Blood samples were taken from healthy volunteers. Platelet aggregation experiments were performed using washed platelets from human blood freshly collected in citrate as an anticoagulant, as previously described (38). Breast or ovarian cancer cells (4 × 10 6 cells) previously cultured in the absence or in the presence of doxycycline were added to washed human platelets (4 × 10 5 platelets/μl) in a final volume of 400 μl under stirring conditions at 37°C.…”

The role of platelet activation in tumor metastasis

“…Activated platelets secrete gelatinase A [80], heparanase [81], and induce the release of gelatinase and urokinase (u-PA) by endothelial cells and tumor cells in vitro [82]. The role of platelet-derived microparticles (PMV), which are circular fragments shed by activated platelets, was analyzed for its potential to contribute to metastasis [83,84].…”